We examined the influence of glutethione (GSH) on the expression of murine CD8 in splenic lymphocytes of young and old mice. Flow cytometric analysis showed that the murine lymphocytes exhibited 3 subpopulations with low, medium and high fluorescence intensity after labeling with fluorescein isothiocyanate-labeled anti-murine CD8 antibodies. Culture of lymphocytes of young mice (3 months) with GSH (1 mg/ml) for 48-72 h increased (from 3.2 +/- 0.2% to 10.6+/- 0.3%; p< 0.005) the proportion of cells with high fluorescence intensity, while that of the cells with medium intensity was unchanged. When lymphocytes of cells with high fluorescence intensity was not significantly changed (3.53% vs 3.46%), while that of cells with medium intensity was increased (from 14 +/- 0.4% to 19 +/- 0.4%; p < 0.05). These results suggest that GSH potentiates the expression of CD8 receptors. In the presence of GSH, the GSH sensitive CD8+-cells of young mice have a higher CDS receptor density than those of old mice. Since we have previously found low GSH levels in whole blood of human immunodeficiency virus-seropositive persons, these studies provide indirect support for the hypothesis that the decline of cellular response to GSH or the depletion of GSH may contribute to the immune dysfunction in aged animals of animals suffering from acquired immunodeficiency.